A Review on the Role of Phytoconstituents Chrysin on the Protective Effect
on Liver and Kidney

Debika      Sarmah; Rupa      Sengupta

Abstract

Background: The chance of contracting significant diseases increases due to an unhealthy and contemporary lifestyle. Chrysin is a flavonoid of the flavone class in numerous plants, including Passiflora and Pelargonium. Chrysin has long been used to treat a variety of illnesses. Chrysin, an essential flavonoid, has many pharmacological actions, including anticancer, antiviral, anti-inflammatory, anti-arthritic, depressive, hypolipidemic, hepatoprotective, and nephroprotective activity.

Purpose: This explorative review was commenced to provide a holistic review of flavonoids confirming that Chrysin has a therapeutic potential on the liver and kidney and reduces the hepatotoxicity and nephrotoxicity induced by diverse toxicants, which can be helpful for the toxicologists, pharmacologists, and chemists to develop new safer pharmaceutical products with chrysin and other toxicants.

Study Design: The most relevant studies that were well-explained and fit the chosen topic best were picked. The achieved information was analyzed to determine the outcome by screening sources by title, abstract, and whole work. Between themselves, the writers decided on the studies to be considered. The necessary details were systematically organized into titles and subtitles and compressively discussed.

Method: The information presented in this review is obtained using targeted searches on several online platforms, including Google Scholar, Scifinder, PubMed, Science Direct, ACS publications, and Wiley Online Library. The works were chosen based on the inclusion criteria agreed upon by all authors.

Results: Chrysin is a promising bioactive flavonoid with significant health benefits, and its synthetic replacements are being utilized as pharmaceuticals to treat various diseases. Findings revealed that Chrysin exhibits hepatoprotective actions against several hepatotoxicants like 2,3,7,8 tetrachlorodibenzo- p-dioxin, carbon tetrachloride (CCl₄), cisplatin, and others by lowering the levels of liver toxicity biomarkers and enhancing antioxidant levels. Additionally, chrysin has potential nephroprotective properties against various nephrotoxicants, like Cisplatin, Doxorubicin, Paracetamol, Gentamicin, Streptazosin, and others by dropping kidney toxicity marker levels, reducing oxidative stress, and improving the antioxidant level.

Conclusion: According to this revised study, chrysin is a promising phytoconstituent that can be utilized as an alternate treatment for various medications that cause hepatotoxicity and nephrotoxicity. With active chrysin, several dosage forms targeting the liver and kidneys can be formulated.

Graphical Abstract

[1]
Parfait BTS, Lawrence MTJ. Pharmacognosy, Phytotherapy and Modern Medicine. Int Jr Infect Dis & Epidemlgy  2023; 23(4): 1.

[2]
Panche AN, Diwan AD, Chandra SR. Flavonoids: An overview. J Nutr Sci  2016; 5: e47.
 [http://dx.doi.org/10.1017/jns.2016.41] [PMID:  28620474]

[3]
Mani R, Natesan V. Chrysin: Sources, beneficial pharmacological activities, and molecular mechanism of action. Phytochemistry  2018; 145: 187-96.
 [http://dx.doi.org/10.1016/j.phytochem.2017.09.016] [PMID:  29161583]

[4]
Anandhi R, Annadurai T, Anitha TS, et al. Antihypercholesterolemic and antioxidative effects of an extract of the oyster mushroom, Pleurotus ostreatus, and its major constituent, chrysin, in Triton WR-1339-induced hypercholesterolemic rats. J Physiol Biochem  2013; 69(2): 313-23.
 [http://dx.doi.org/10.1007/s13105-012-0215-6] [PMID:  23104078]

[5]
Balta C, Herman H, Boldura OM, et al. Chrysin attenuates liver fibrosis and hepatic stellate cell activation through TGF-β/Smad signaling pathway. Chem Biol Interact  2015; 240: 94-101.
 [http://dx.doi.org/10.1016/j.cbi.2015.08.013] [PMID:  26297989]

[6]
Durak MA, Öztanir MN, Başak Türkmen N, et al. Chrysin prevents brain damage caused by global cerebralischemia/reperfusion in a C57BL/J6 mouse model. Turk J Med Sci  2016; 46(6): 1926-33.
 [http://dx.doi.org/10.3906/sag-1508-119] [PMID:  28081349]

[7]
Khan R, Khan AQ, Qamar W, et al. Chrysin protects against cisplatin-induced colon. toxicity via amelioration of oxidative stress and apoptosis: Probable role of p38MAPK and p53. Toxicol Appl Pharmacol  2012; 258(3): 315-29.
 [http://dx.doi.org/10.1016/j.taap.2011.11.013] [PMID:  22155348]

[8]
Muñoz VA, Ferrari GV, Sancho MI, Montaña MP. Spectroscopic and thermodynamic study of chrysin and quercetin complexes with Cu (II). J Chem Eng Data  2016; 61(2): 987-95.
 [http://dx.doi.org/10.1021/acs.jced.5b00837]

[9]
Samarghandian S, Azimi-Nezhad M, Samini F, Farkhondeh T. Chrysin treatment improves diabetes and its complications in liver, brain, and pancreas in streptozotocin-induced diabetic rats. Can J Physiol Pharmacol  2016; 94(4): 388-93.
 [http://dx.doi.org/10.1139/cjpp-2014-0412] [PMID:  26863330]

[10]
Balunas MJ, Kinghorn AD. Drug discovery from medicinal plants. Life Sci  2005; 78(5): 431-41.
 [http://dx.doi.org/10.1016/j.lfs.2005.09.012] [PMID:  16198377]

[11]
Rana AC, Gulliya B. Chemistry and pharmacology of flavonoids-a review. Indian J Pharm Educ Res  2019; 53(1): 8-20.
 [http://dx.doi.org/10.5530/ijper.53.1.3]

[12]
Burak M, Imen Y. Flavonoids and their antioxidant properties. Turk Klin Tip Bilim Derg  1999; 19: 296-304.

[13]
Castañeda-Ovando A, Pacheco-Hernández ML, Páez-Hernández ME, Rodríguez JA, Galán-Vidal CA. Chemical studies of anthocyanins: A review. Food Chem  2009; 113(4): 859-71.
 [http://dx.doi.org/10.1016/j.foodchem.2008.09.001]

[14]
Havsteen BH. The biochemistry and medical significance of the flavonoids. Pharmacol Ther  2002; 96(2-3): 67-202.
 [http://dx.doi.org/10.1016/S0163-7258(02)00298-X] [PMID:  12453566]

[15]
Walker EH, Pacold ME, Perisic O, et al. Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol Cell  2000; 6(4): 909-19.
 [http://dx.doi.org/10.1016/S1097-2765(05)00089-4] [PMID:  11090628]

[16]
Griesbach RJ. Biochemistry and genetics of flower color. Plant Breed Rev  2010; 25: 89-114.

[17]
Banjarnahor SDS, Artanti N. Antioxidant properties of flavonoids. Med J Indones  2015; 23(4): 239-44.
 [http://dx.doi.org/10.13181/mji.v23i4.1015]

[18]
Nicole Cotelle BSP. Role of flavonoids in oxidative stress. Curr Top Med Chem  2001; 1(6): 569-90.
 [http://dx.doi.org/10.2174/1568026013394750] [PMID: 11895132]

[19]
Pietta PG. Flavonoids as antioxidants. J Nat Prod  2000; 63(7): 1035-42.
 [http://dx.doi.org/10.1021/np9904509] [PMID:  10924197]

[20]
Russo D. Flavonoids and the structure-antioxidant activity relationship. J Pharmacogn Nat Prod  2018; 4(1): e109.
 [http://dx.doi.org/10.4172/2472-0992.1000e109]

[21]
Tahir M, Sultana S. Chrysin modulates ethanol metabolism in Wistar rats: A promising role against organ toxicities. Alcohol Alcohol  2011; 46(4): 383-92.
 [http://dx.doi.org/10.1093/alcalc/agr038] [PMID:  21531755]

[22]
Tapas AR, Sakarkar DM, Kakde RB. Flavonoids as nutraceuticals: A review. Trop J Pharm Res  2008; 7(3): 1089-99.
 [http://dx.doi.org/10.4314/tjpr.v7i3.14693]

[23]
Iwashina T. The structure and distribution of the flavonoids in plants. J Plant Res  2000; 113(3): 287-99.
 [http://dx.doi.org/10.1007/PL00013940]

[24]
Trauner M, Meier PJ, Boyer JL. Molecular pathogenesis of cholestasis. N Engl J Med  1998; 339(17): 1217-27.
 [http://dx.doi.org/10.1056/NEJM199810223391707] [PMID:  9780343]

[25]
Alzand KI, Mohamed MA. Flavonoids: Chemistry, biochemistry, and antioxidant activity. J Pharm Res  2012; 5(40134012): 37.

[26]
Tsao R, McCallum J. Chemistry of flavonoids. In: Fruit and vegetable phytochemicals: chemistry, nutritional value and stability.   2009; 5: pp. 131-53.

[27]
Seshadri TR. Recent developments in the chemistry of flavonoids. Tetrahedron  1959; 6(3): 169-200.
 [http://dx.doi.org/10.1016/0040-4020(59)80001-6]

[28]
Berk Ş, Kaya S, Akkol EK, Bardakçı H. A comprehensive and current review on the role of flavonoids in lung cancer–Experimental and theoretical approaches. Phytomedicine  2022; 98: 153938.
 [http://dx.doi.org/10.1016/j.phymed.2022.153938] [PMID:  35123170]

[29]
Mendes APS, Borges RS, Neto AMJC, de Macedo LGM, da Silva ABF. The basic antioxidant structure for flavonoid derivatives. J Mol Model  2012; 18(9): 4073-80.
 [http://dx.doi.org/10.1007/s00894-012-1397-0] [PMID:  22527272]

[30]
Novza YA, Popova EM. Flavonoids: Chemistry and biological activities. Problems of Environmental Biotechnology  2016; 1: 1-10.

[31]
Narayana KR, Reddy MS, Chaluvadi MR, Krishna DR. Bioflavonoids classification, pharmacological, biochemical effects and therapeutic potential. Indian J Pharmacol  2001; 33(1): 2-16.

[32]
Santos EL, Maia BHLNS, Ferriani AP, Teixeira SD. Flavonoids: Classification, biosynthesis and chemical ecology. In: Flavonoids- From biosynthesis to human health. intechopen.   2017; 13: pp. 78-94.

[33]
Brodowska KM. Natural flavonoids: Classification, potential role, and application of flavonoid analogues. Eur J Biol Res  2017; 7(2): 108-23.

[34]
Shen N, Wang T, Gan Q, Liu S, Wang L, Jin B. Plant flavonoids: Classification, distribution, biosynthesis, and antioxidant activity. Food Chem  2022; 383: 132531.
 [http://dx.doi.org/10.1016/j.foodchem.2022.132531] [PMID:  35413752]

[35]
Claudine M, Augustin S, Christine M, Christian R, Liliana J. Polyphenols: Food sources and bioavailability. Am J Clin Nutr  2004; 79(5): 727-47.

[36]
Iwashina T. Flavonoid properties of five families newly incorporated into the order Caryophyllales. Bull Natl Mus Nat Sci  2013; 39: 25-51.

[37]
Matthies A, Clavel T, Gütschow M, et al. Conversion of daidzein and genistein by an anaerobic bacterium newly isolated from the mouse intestine. Appl Environ Microbiol  2008; 74(15): 4847-52.
 [http://dx.doi.org/10.1128/AEM.00555-08] [PMID:  18539813]

[38]
Aoki T, Akashi T, Ayabe S. Flavonoids of leguminous plants: Structure, biological activity, and biosynthesis. J Plant Res  2000; 113(4): 475-88.
 [http://dx.doi.org/10.1007/PL00013958]

[39]
Iinuma M, Tanaka T, Hamada K, et al. Revised structure of neoflavone in Coutarea hexandra. Phytochemistry  1987; 26(11): 3096-7.
 [http://dx.doi.org/10.1016/S0031-9422(00)84609-9]

[40]
Nishimuta S, Taki M, Takaishi S, Iijima Y, Akiyama T. Structures of 4-aryl-coumarin (neoflavone) dimers isolated from Pistacia chinensis BUNGE and their estrogen-like activity. Chem Pharm Bull  2000; 48(4): 505-8.
 [http://dx.doi.org/10.1248/cpb.48.505] [PMID:  10783069]

[41]
Hertog MGL, Hollman PCH, van de Putte B. Content of potentially anticarcinogenic flavonoids of tea infusions, wines, and fruit juices. J Agric Food Chem  1993; 41(8): 1242-6.
 [http://dx.doi.org/10.1021/jf00032a015]

[42]
Justesen U, Knuthsen P. Composition of flavonoids in fresh herbs and calculation of flavonoid intake by use of herbs in traditional Danish dishes. Food Chem  2001; 73(2): 245-50.
 [http://dx.doi.org/10.1016/S0308-8146(01)00114-5]

[43]
Sreedevi AUU, Koganti B. Effect of chrysin isolated from Oroxylum indicum against cisplatin-induced acute renal failure 

[44]
Stewart AJ, Bozonnet S, Mullen W, Jenkins GI, Lean MEJ, Crozier A. Occurrence of flavonols in tomatoes and tomato-based products. J Agric Food Chem  2000; 48(7): 2663-9.
 [http://dx.doi.org/10.1021/jf000070p] [PMID:  10898604]

[45]
Naz S, Imran M, Rauf A, et al. Chrysin: Pharmacological and therapeutic properties. Life Sci  2019; 235: 116797.
 [http://dx.doi.org/10.1016/j.lfs.2019.116797] [PMID:  31472146]

[46]
Kao YC, Zhou C, Sherman M, Laughton CA, Chen S. Molecular basis of the inhibition of human aromatase (estrogen synthetase) by flavone and isoflavone phytoestrogens: A site-directed mutagenesis study. Environ Health Perspect  1998; 106(2): 85-92.
 [http://dx.doi.org/10.1289/ehp.9810685] [PMID:  9435150]

[47]
Koltay M. Isolation and identification of constituents of propolis. A thesis of department science 1981.

[48]
Pichichero E, Cicconi R, Mattei M, Muzi MG, Canini A. Acacia honey and chrysin reduce proliferation of melanoma cells through alterations in cell cycle progression. Int J Oncol  2010; 37(4): 973-81.
 [PMID:  20811719]

[49]
Talebi M, Talebi M, Farkhondeh T, et al. An updated review on the versatile role of chrysin in neurological diseases: Chemistry, phar-macology, and drug delivery approaches. Biomed Pharmacother  2021; 141: 111906.
 [http://dx.doi.org/10.1016/j.biopha.2021.111906] [PMID:  34328092]

[50]
Blasco C, Vazquez-Roig P, Onghena M, Masia A, Picó Y. Analysis of insecticides in honey by liquid chromatography–ion trap-mass spectrometry: Comparison of different extraction procedures. J Chromatogr A  2011; 1218(30): 4892-901.
 [http://dx.doi.org/10.1016/j.chroma.2011.02.045] [PMID:  21411107]

[51]
Dhawan K, Kumar S, Sharma A. Beneficial effects of chrysin and benzoflavone on virility in 2-year-old male rats. J Med Food  2002; 5(1): 43-8.
 [http://dx.doi.org/10.1089/109662002753723214] [PMID:  12511112]

[52]
Brown E, Hurd NS, McCall S, Ceremuga TE. Evaluation of the anxiolytic effects of chrysin, a Passiflora incarnata extract, in the labora-tory rat. AANA J  2007; 75(5): 333-7.
 [PMID:  17966676]

[53]
Chaudhary AK, Harminder  , Singh V. A Review on the taxonomy, ethnobotany, chemistry and pharmacology of Oroxylum indicum vent. Indian J Pharm Sci  2011; 73(5): 483-90.
 [http://dx.doi.org/10.4103/0250-474X.98981] [PMID:  22923859]

[54]
Pereira OR, Silva AMS, Domingues MRM, Cardoso SM. Identification of phenolic constituents of Cytisus multiflorus. Food Chem  2012; 131(2): 652-9.
 [http://dx.doi.org/10.1016/j.foodchem.2011.09.045]

[55]
Dewi RM, Megawati M, Antika LD. Antidiabetic properties of dietary chrysin: A cellular mechanism review. Mini Rev Med Chem  2022; 22(10): 1450-7.
 [http://dx.doi.org/10.2174/1389557521666211101162449] [PMID:  34720081]

[56]
Castañeda-Arriaga R, Marino T, Russo N, Alvarez-Idaboy JR, Galano A. Chalcogen effects on the primary antioxidant activity of chrysin and quercetin. New J Chem  2020; 44(21): 9073-82.
 [http://dx.doi.org/10.1039/D0NJ01795G]

[57]
Zarzecki MS, Araujo SM, Bortolotto VC, de Paula MT, Jesse CR, Prigol M. Hypolipidemic action of chrysin on Triton WR-1339-induced hyperlipidemia in female C57BL/6 mice. Toxicol Rep  2014; 1: 200-8.
 [http://dx.doi.org/10.1016/j.toxrep.2014.02.003] [PMID:  28962239]

[58]
Lotfi-Attari J, Pilehvar-Soltanahmadi Y, Dadashpour M, et al. Co-delivery of curcumin and chrysin by polymeric nanoparticles inhibit synergistically growth and hTERT gene expression in human colorectal cancer cells. Nutr Cancer  2017; 69(8): 1290-9.
 [http://dx.doi.org/10.1080/01635581.2017.1367932] [PMID:  29083232]

[59]
Kasala ER, Bodduluru LN, Madana RM, v AK, Gogoi R, Barua CC. Chemopreventive and therapeutic potential of chrysin in cancer: Mechanistic perspectives. Toxicol Lett  2015; 233(2): 214-25.
 [http://dx.doi.org/10.1016/j.toxlet.2015.01.008] [PMID:  25596314]

[60]
Hermenean A, Mariasiu T, Navarro-González I, et al. Hepatoprotective activity of chrysin is mediated through TNF-α in chemically-induced acute liver damage: An in vivo study and molecular modeling. Exp Ther Med  2017; 13(5): 1671-80.
 [http://dx.doi.org/10.3892/etm.2017.4181] [PMID:  28565752]

[61]
Pingili RB, Pawar AK, Challa SR, Kodali T, Koppula S, Toleti V. A comprehensive review on hepatoprotective and nephroprotective activities of chrysin against various drugs and toxic agents. Chem Biol Interact  2019; 308: 51-60.
 [http://dx.doi.org/10.1016/j.cbi.2019.05.010] [PMID:  31085170]

[62]
Zager RA. Pathogenetic mechanisms in nephrotoxic acute renal failure. Semin Nephrol  1997; 17(1): 3-14.
 [PMID:  9000545]

[63]
Darwish HA, Arab HH, Abdelsalam RM. Chrysin alleviates testicular dysfunction in adjuvant arthritic rats via suppression of inflamma-tion and apoptosis: Comparison with celecoxib. Toxicol Appl Pharmacol  2014; 279(2): 129-40.
 [http://dx.doi.org/10.1016/j.taap.2014.05.018] [PMID:  24932515]

[64]
Uhl M, Ecker S, Kassie F, et al. Effect of chrysin, a flavonoid compound, on the mutagenic activity of 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) and benzo(a)pyrene (B(a)P) in bacterial and human hepatoma (HepG2) cells. Arch Toxicol  2003; 77(8): 477-84.
 [http://dx.doi.org/10.1007/s00204-003-0469-4] [PMID:  12856103]

[65]
Rodríguez-Landa JF, German-Ponciano LJ, Puga-Olguín A, Olmos-Vázquez OJ. Pharmacological, neurochemical, and behavioral mechanisms underlying the anxiolytic- and antidepressant-like effects of flavonoid chrysin. Molecules  2022; 27(11): 3551.
 [http://dx.doi.org/10.3390/molecules27113551] [PMID:  35684488]

[66]
Wallace MA. Anatomy and physiology of the kidney. AORN J  1998; 68(5): 799-820.
 [http://dx.doi.org/10.1016/S0001-2092(06)62377-6] [PMID:  9829131]

[67]
Abdel-Misih SRZ, Bloomston M. Liver Anatomy. Surg Clin North Am  2010; 90(4): 643-53.
 [http://dx.doi.org/10.1016/j.suc.2010.04.017] [PMID:  20637938]

[68]
Juza RM, Pauli EM. Clinical and surgical anatomy of the liver: A review for clinicians. Clin Anat  2014; 27(5): 764-9.
 [http://dx.doi.org/10.1002/ca.22350] [PMID:  24453062]

[69]
McCuskey R. Anatomy of the liver. In: Zakim and Boyer’s Hepatology: a textbook of liver disease.   2012; 6: pp. 3-19.

[70]
Sharma A, Chakraborti KK, Handa SS. Antihepatotoxic activity of some Indian herbal formulations as compared to silymarin. Fitoterapia  1991; 62: 229-35.

[71]
Jothy SL, Zakaria Z, Chen Y, Lau YL, Latha LY, Sasidharan S. Acute oral toxicity of methanolic seed extract of Cassia fistula in mice. Molecules  2011; 16(6): 5268-82.
 [http://dx.doi.org/10.3390/molecules16065268] [PMID:  21701437]

[72]
Pandit A, Sachdeva T, Bafna P. Drug-induced hepatotoxicity: A review. J Appl Pharm Sci  2012; 2(05): 233-43.

[73]
Ostapowicz G, Fontana RJ, Schiødt FV, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med  2002; 137(12): 947-54.
 [http://dx.doi.org/10.7326/0003-4819-137-12-200212170-00007] [PMID:  12484709]

[74]
Gressner AM. Liver fibrosis: Perspectives in pathobiochemical research and clinical outlook. Eur J Clin Chem Clin Biochem  1991; 29(5): 293-311.
 [PMID:  1892952]

[75]
Ahsan R, Islam KM, Musaddik A, Haque E. Hepatoprotective activity of methanol extract of some medicinal plants against carbon tetrachloride induced hepatotoxicity in albino rats. Glob J Pharmacol  2009; 3(3): 116-22.

[76]
Lee WM. Drug-induced hepatotoxicity. N Engl J Med  2003; 349(5): 474-85.
 [http://dx.doi.org/10.1056/NEJMra021844] [PMID:  12890847]

[77]
Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ. Mechanisms of hepatotoxicity. Toxicol Sci  2002; 65(2): 166-76.
 [http://dx.doi.org/10.1093/toxsci/65.2.166] [PMID:  11812920]

[78]
Bissell D, Gores GJ, Laskin DL, Hoofnagle JH. Drug-induced liver injury: Mechanisms and test systems. Hepatology  2001; 33(4): 1009-13.
 [http://dx.doi.org/10.1053/jhep.2001.23505] [PMID:  11283870]

[79]
Cullen JM. Mechanistic classification of liver injury. Toxicol Pathol  2005; 33(1): 6-8.
 [http://dx.doi.org/10.1080/01926230590522428] [PMID:  15805050]

[80]
Wang K, Lin B. Pathophysiological significance of hepatic apoptosis. ISRN Hepatol  2012; 2013: 740149.
 [PMID:  27335822]

[81]
Wang J, Zhang T, Du J, Cui S, Yang F, Jin Q. Anti-enterovirus 71 effects of chrysin and its phosphate ester. PLoS One  2014; 9(3): e89668.
 [http://dx.doi.org/10.1371/journal.pone.0089668] [PMID:  24598537]

[82]
Faubion WA, Guicciardi ME, Miyoshi H, et al. Toxic bile salts induce rodent hepatocyte apoptosis via direct activation of Fas. J Clin Invest  1999; 103(1): 137-45.
 [http://dx.doi.org/10.1172/JCI4765] [PMID:  9884343]

[83]
Pessayre D, Mansouri A, Haouzi D, Fromenty B. Hepatotoxicity due to mitochondrial dysfunction. Cell Biol Toxicol  1999; 15(6): 367-73.
 [http://dx.doi.org/10.1023/A:1007649815992] [PMID:  10811531]

[84]
Geubel AP, Sempoux CL. Drug and toxin-induced bile duct disorders. J Gastroenterol Hepatol  2000; 15(11): 1232-8.
 [PMID:  11129214]

[85]
Harsh M. Textbook of Pathology.  New Delhi: Jaypee Brothers: Medical Publishers (P) Ltd. 2005; pp. 22-4.

[86]
Ciftci O, Vardi N, Ozdemir I. Effects of quercetin and chrysin on 2,3,7,8-tetrachlorodibenzo- p -dioxin induced hepatotoxicity in rats. Environ Toxicol  2013; 28(3): 146-54.
 [http://dx.doi.org/10.1002/tox.20707] [PMID:  21544919]

[87]
Anand KV, Anandhi R, Pakkiyaraj M, Geraldine P. Protective effect of chrysin on carbon tetrachloride (CCl 4)—induced tissue injury in male Wistar rats. Toxicol Ind Health  2011; 27(10): 923-33.
 [http://dx.doi.org/10.1177/0748233711399324] [PMID:  21511893]

[88]
Rehman MU, Ali N, Rashid S, et al. Alleviation of hepatic injury by chrysin in cisplatin administered rats: Probable role of oxidative and inflammatory markers. Pharmacol Rep  2014; 66(6): 1050-9.
 [http://dx.doi.org/10.1016/j.pharep.2014.06.004] [PMID:  25443734]

[89]
Pushpavalli G, Kalaiarasi P, Veeramani C, Pugalendi KV. Effect of chrysin on hepatoprotective and antioxidant status in d-galactosamine-induced hepatitis in rats. Eur J Pharmacol  2010; 631(1-3): 36-41.
 [http://dx.doi.org/10.1016/j.ejphar.2009.12.031] [PMID:  20056116]

[90]
Rashid S, Ali N, Nafees S, et al. Alleviation of doxorubicin-induced nephrotoxicity and hepatotoxicity by chrysin in Wistar rats. Toxicol Mech Methods  2013; 23(5): 337-45.
 [http://dx.doi.org/10.3109/15376516.2012.759306] [PMID:  23256457]

[91]
Sathiavelu J, Senapathy GJ, Devaraj R, Namasivayam N. Hepatoprotective effect of chrysin on prooxidant-antioxidant status during ethanol-induced toxicity in female albino rats. J Pharm Pharmacol  2010; 61(6): 809-17.
 [http://dx.doi.org/10.1211/jpp.61.06.0015] [PMID:  19505373]

[92]
Mizar SM, Omar HA, El Sherbiny GA, El-moselhy MA. Nebivolol and chrysin protect the liver against ischemia/reperfusion-induced injury in rats. Beni Suef Univ J Basic Appl Sci  2015; 4(1): 86-92.
 [http://dx.doi.org/10.1016/j.bjbas.2015.02.012]

[93]
Eldutar E, Kandemir FM, Kucukler S, Caglayan C. Restorative effects of Chrysin pretreatment on oxidant–antioxidant status, inflammato-ry cytokine production, and apoptotic and autophagic markers in acute paracetamol‐induced hepatotoxicity in rats: An experimental and biochemical study. J Biochem Mol Toxicol  2017; 31(11): e21960.
 [http://dx.doi.org/10.1002/jbt.21960] [PMID:  28682524]

[94]
Khan MS, Devaraj H, Devaraj N. Chrysin abrogates early hepatocarcinogenesis and induces apoptosis in N-nitrosodiethylamine-induced preneoplastic nodules in rats. Toxicol Appl Pharmacol  2011; 251(1): 85-94.
 [http://dx.doi.org/10.1016/j.taap.2010.12.004] [PMID:  21167192]

[95]
Ali N, Rashid S, Nafees S, Hasan SK, Sultana S. Beneficial effects of Chrysin against Methotrexate-induced hepatotoxicity via attenuation of oxidative stress and apoptosis. Mol Cell Biochem  2014; 385(1-2): 215-23.
 [http://dx.doi.org/10.1007/s11010-013-1830-4] [PMID:  24154663]

[96]
Mani R, Natesan V, Arumugam R. Hepatoprotective effect of Chrysin on Ammonium chloride induced hyperammonemia via attenuating liver damage in male albino Wistar rats. Int J Modn Res Revs  2016; 4(11): 1414-20.

[97]
Huang CS, Lii CK, Lin AH, et al. Protection by chrysin, apigenin, and luteolin against oxidative stress is mediated by the Nrf2-dependent up-regulation of heme oxygenase 1 and glutamate cysteine ligase in rat primary hepatocytes. Arch Toxicol  2013; 87(1): 167-78.
 [http://dx.doi.org/10.1007/s00204-012-0913-4] [PMID:  22864849]

[98]
El-Marasy SA, El Awdan SA, Abd-Elsalam RM. Protective role of chrysin on thioacetamide-induced hepatic encephalopathy in rats. Chem Biol Interact  2019; 299: 111-9.
 [http://dx.doi.org/10.1016/j.cbi.2018.11.021] [PMID:  30500344]

[99]
He Y, Xia Z, Yu D, et al. Hepatoprotective effects and structure-activity relationship of five flavonoids against lipopolysaccharide/d-galactosamine induced acute liver failure in mice. Int Immunopharmacol  2019; 68: 171-8.
 [http://dx.doi.org/10.1016/j.intimp.2018.12.059] [PMID:  30641432]

[100]
Gattone V H. Effect of chrysin, a flavonoid compound, on the mutagenic activity of 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyri-dine (PhIP) and benzo (a) pyrene (B (a) P) in bacterial and human hepatoma (HepG2) cells. Arch Toxicol  2007; 77(8): 477-84.
 [http://dx.doi.org/10.1096/fasebj.21.5.A2-d]

[101]
Naughton CA. Drug-induced nephrotoxicity. Am Fam Physician  2008; 78(6): 743-50.
 [PMID:  18819242]

[102]
Schoolwerth AC, Sica DA, Ballermann BJ, Wilcox CS. Renal considerations in angiotensin converting enzyme inhibitor therapy: A statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association. Circulation  2001; 104(16): 1985-91.
 [http://dx.doi.org/10.1161/hc4101.096153] [PMID:  11602506]

[103]
Lamas S. Cellular mechanisms of vascular injury mediated by calcineurin inhibitors. Kidney Int  2005; 68(2): 898-907.
 [http://dx.doi.org/10.1111/j.1523-1755.2005.00472.x] [PMID:  16014073]

[104]
Markowitz GS, Perazella MA. Drug-induced renal failure: a focus on tubulointerstitial disease. Clin Chim Acta  2005; 351(1-2): 31-47.
 [http://dx.doi.org/10.1016/j.cccn.2004.09.005] [PMID:  15563870]

[105]
Coco TJ, Klasner AE. Drug-induced rhabdomyolysis. Curr Opin Pediatr  2004; 16(2): 206-10.
 [http://dx.doi.org/10.1097/00008480-200404000-00017] [PMID:  15021204]

[106]
Pisoni R, Ruggenenti P, Remuzzi G. Drug-induced thrombotic microangiopathy: incidence, prevention and management. Drug Saf  2001; 24(7): 491-501.
 [http://dx.doi.org/10.2165/00002018-200124070-00002] [PMID:  11444722]

[107]
Manor SM, Guillory GS, Jain SP. Clopidogrel-induced thrombotic thrombocytopenic purpura-hemolytic uremic syndrome after coronary artery stenting. Pharmacotherapy  2004; 24(5): 664-7.
 [http://dx.doi.org/10.1592/phco.24.6.664.34732] [PMID:  15162901]

[108]
Sultana S, Verma K, Khan R. Nephroprotective efficacy of chrysin against cisplatin-induced toxicity via attenuation of oxidative stress. J Pharm Pharmacol  2012; 64(6): 872-81.
 [http://dx.doi.org/10.1111/j.2042-7158.2012.01470.x] [PMID:  22571266]

[109]
Mukherjee A, Kandhare A D, Bodhankar S L. Effect of chrysin on gentamicin-induced nephrotoxicity in laboratory animals. Pharmaco-logia  2016; 7(6-7): 296-307.

[110]
Premalatha M, Parameswari CS. Renoprotective effect of chrysin (5, 7 dihydroxy flavone) in streptozotocin induced diabetic nephropa-thy in rats. Int J Pharm Pharm Sci  2012; 4(3): 241-7.

[111]
Rehman MU, Tahir M, Khan AQ, et al. Chrysin suppresses renal carcinogenesis via amelioration of hyperproliferation, oxidative stress and inflammation: Plausible role of NF-κB. Toxicol Lett  2013; 216(2-3): 146-58.
 [http://dx.doi.org/10.1016/j.toxlet.2012.11.013] [PMID:  23194824]

[112]
Rashid S, Ali N, Nafees S, Hasan SK, Sultana S. Mitigation of 5-Fluorouracil induced renal toxicity by chrysin via targeting oxidative stress and apoptosis in wistar rats. Food Chem Toxicol  2014; 66: 185-93.
 [http://dx.doi.org/10.1016/j.fct.2014.01.026] [PMID:  24486618]

[113]
Sreedevi Adikay U U, Koganti B. Effect of chrysin isolated from Oroxylum indicum against cisplatin-induced acute renal failure 

[114]
Ali BH, Al Za’'abi M, Adham SA, Yasin J, Nemmar A, Schupp N. Therapeutic effect of chrysin on adenine-induced chronic kidney disease in rats. Cell Physiol Biochem  2016; 38(1): 248-57.
 [http://dx.doi.org/10.1159/000438626] [PMID:  26784294]

[115]
Tatli Seven P, Gül Baykalir B, Seven İ, Parlak Ak T, Başak N, Güllüoğlu H. The protective effects of chrysin and flunixin meglumine against excess copper in male rats. Turk J Vet Anim Sci  2018; 42(5): 376-87.
 [http://dx.doi.org/10.3906/vet-1710-70]

[116]
Hanedan B, Ozkaraca M, Kirbas A, et al. Investigation of the effects of hesperidin and chrysin on renal injury induced by colistin in rats. Biomed Pharmacother  2018; 108: 1607-16.
 [http://dx.doi.org/10.1016/j.biopha.2018.10.001] [PMID:  30372863]

[117]
Thekkumalai M, Ramanathan V. Role of chrysin on hepatic and renal activities of N ω -nitro-l-arginine-methylester induced hypertensive rats. Int J Nutr Pharmacol Neurol Dis  2014; 4(1): 58.
 [http://dx.doi.org/10.4103/2231-0738.124615]

[118]
Gambelunghe C, Rossi R, Sommavilla M, et al. Effects of chrysin on urinary testosterone levels in human males. J Med Food  2003; 6(4): 387-90.
 [http://dx.doi.org/10.1089/109662003772519967] [PMID:  14977449]

Cite As

Current Drug Discovery Technologies

A Review on the Role of Phytoconstituents Chrysin on the Protective Effect on Liver and Kidney

Abstract

Graphical Abstract